Centrifugation pheresis system

ABSTRACT

A system and method of separation of therapeutic components from blood. The system includes a dual member centrifuge and a disposable single use fluid transfer set. The set includes an elongated flexible separation chamber having an input port, a separated component output port and a residual fluid output port. The input port and the separated component output ports are located at opposite ends of the elongated separation chamber. The centrifuge includes a receiving chamber with a selectively formed annular slot therein. The separation chamber is positioned in the annularly shaped slot and rotated at a predetermined rotational velocity. Fluids such as whole blood flows through the separation chamber and are separated into various therapeutic components such as platelet rich plasma and residual concentrated red blood cells. Platelet rich plasma can be drawn off as the separated therapeutic component. An alternate two part transfer set provides for highly efficient platelet pheresis. The platelet rich plasma is separated from the residual red blood cells in a first part. The platelet rich plasma flows into the second part and is separated into platelet poor plasma and platelets. The platelet poor plasma can be drawn off and returned to a donor or collected. The platelet concentrate can then be accumulated in a separate container.

This is a divisional of application Ser. No. 07/748,244 filed Aug. 21,1991, now U.S. Pat. No. 5,322,620, which is a continuation ofapplication Ser. No. 07/514,995 filed May 26, 1989 (now U.S. Pat. No.5,104,526), which is a continuation of application Ser. No. 07/009,179filed Jan. 30, 1987 (now U.S. Pat. No. 4,834,890).

TECHNICAL FIELD

The invention pertains to the field of blood component separation andcollection. More particularly, the invention pertains to the collectionof platelets or plasma from volunteer donors at temporary sites, remotefrom medical facilities, with portable lightweight equipment capable ofeasy transport.

BACKGROUND OF THE INVENTION

The collection of blood from volunteer donors has become a verysuccessful and very refined activity. The development of single needle,single use, disposable blood collection sets has provided a safe,relatively inexpensive and donor comfortable medium for use in the bloodcollection process. Such sets have made possible large-scale collectionof blood from volunteer donors at sites such as church halls, schools oroffices which might be remote from medical facilities. The availabilityof volunteer donors is important in that such donors tend to berelatively healthy. In addition, they provide a potentially much largerreservoir of donarable blood than is available from the available groupof paid donors.

In recent years, processing of whole blood from a donor has come toroutinely include separating the blood into therapeutic components.These components include red blood cells, platelets and plasma. Varioustechniques and apparatus have been developed to facilitate thecollection of whole blood and the subsequent separation of therapeuticcomponents therefrom.

The collection of platelets or plasma from volunteer donors, as opposedto the collection of whole blood, has not been nearly as successful. Asa result, much of the plasma now collected comes from paid donors, asopposed to volunteer donors. It would be very desirable to be able toupgrade the collection of plasma so that it becomes a volunteer basedactivity to a much greater extent than it is currently.

Various methods are known for the collection of platelets or plasma. Forexample, a unit of blood can be drawn from a human donor in aconventional fashion and accumulated in a blood bag or other standardcollection container. This unit of blood can then be processed by acentrifuge to separate the plasma from the other components of the bloodunit. The separated platelets and plasma can subsequently be removedfrom the blood bag. Although allowing all blood components to beharvested, this process has the disadvantage that the donor mustinternally replace the complete unit of blood from which the plasma wasextracted. The replacement process can take 6 to 12 weeks during whichtime the donor cannot again give blood. Further, this process yieldsonly a small portion of available plasma/donor.

In a modification of the above system, plasmapheresis can be performedby centrifugation at the time of donation. The non-plasma portion of theblood is then returned to the donor immediately. While this processallows more frequent donation, often as frequently as once per week, theblood is physically Separated from the donor for centrifugation.

Such physical separation is undesirable because of the cost andcomplexity of systems and procedures that have been developed tominimize the risk of error when several donors are being processedsimultaneously. In addition, physical separation of the blood from thedonor could potentially raise concerns in the collection staff ofexposure to infectous agents in the collected blood if fluid drips orleaks occur.

Separation systems in which the accumulated whole blood is notphysically separated from the donor are also known. These can be eitherbatch or continuous systems.

One continuous centrifuge based system is disclosed in Judson et al.U.S. Pat. No. 3,655,123 entitled "Continuous Flow Blood Separator." Thesystem of the Judson et al. patent uses two needles, an outflow needleand an inflow needle. Whole blood is drawn from a donor via the outflowneedle. The whole blood fills a buffer bag. Blood from the buffer bagdrains, under the force of gravity into a centrifuge. The system of theJudson et al. patent uses the centrifuge to separate blood components.The plasma can be collected in a container. The red blood cells can bereturned to the donor via the inflow needle.

Various systems are known that utilize annular separation chambers forplasma pheresis. For example, U.S. Pat. No. 4,531,932 to Luppin et al.entitled Centrifugal Plasmapheresis Device discloses a system whichincorporates a centrifuge with a rotating annular rotor. A centrallylocated rotating seal couples stationary fluid flow lines to therotating rotor.

Whole blood is drained from a donor, passed through the rotating sealand subjected to separating rotational forces in the rotating rotor.Separated plasma is drawn off and concentrated whole blood cells arepassed back through the rotating seal and returned to the donor.

Related types of systems which incorporate rotatable, disposable annularseparation chambers coupled via rotary seals to stationary tubingmembers are disclosed in U.S. Pat. Nos. 4,387,848; 4,094,461; 4,007,871;and 4,010,894.

One consideration in the processing of whole blood is the requirementthat the processing take place under sterile conditions. A secondconsideration is the requirement that processing take place so as tomaximize storage life. Unless the processing takes place within a singlesealed system, the permitted storage duration and usable lifetime of theblood components is substantially shortened. Components processed withina sealed system can be stored for four to six weeks or longer beforeuse. On the other hand, whole blood or components thereof must be usedwithin 24 hours if the system seal is broken.

To promote the desired ends of sterile processing within a single sealedsystem, a family of dual member centrifuges can be used to effect cellseparation. One example of this type of centrifuge is disclosed in U.S.Pat. No. Re. 29,738 to Adams entitled "Apparatus for Providing EnergyCommunication Between a Moving and a Stationary Terminal."

As is now well known, due to the characteristics of such dual membercentrifuges, it is possible to rotate a container containing a fluid,such as a unit of donated blood and to withdraw a separated fluidcomponent, such as plasma, into a stationary container, outside of thecentrifuge without using rotating seals. Such container systems can beformed as closed, sterile transfer sets.

The Adams patent discloses a centrifuge having an outer rotatable memberand an inner rotatable member. The inner member is positioned within androtatably supported by the outer member.

The outer member rotates at one rotational velocity, usually called oneomega, and the inner rotatably member rotates at twice the rotationalvelocity of the outer housing or two omega. There is thus a one omegadifference in rotational speed of the two members. For purposes of thisdocument, the term "dual member centrifuge" shall refer to centrifugesof the Adams type.

The dual member centrifuge of the Adams patent is particularlyadvantageous in that, as noted above no seals are needed between thecontainer of fluid being rotated and the non-moving component collectioncontainers. The system of the Adams patent, provides a way to processblood into components in a single, sealed, sterile system wherein wholeblood from a donor can be infused into the centrifuge while the twomembers of the centrifuge are being rotated.

An alternate to the apparatus of the Adams patent is illustrated in U.S.Pat. No. 4,056,224 to Lolachi entitled "Flow System for CentrifugalLiquid Processing Apparatus." The system of the Lolachi patent includesa dual member centrifuge of the Adams type. The outer member of theLolachi centrifuge is rotated by a single electric motor which iscoupled to the internal rotatable housing by belts and shafts.

U.S. Pat. No. 4,108,353 to Brown entitled "Centrifugal Apparatus WithOppositely Positioned Rotational Support Means" discloses a centrifugestructure of the Adams type which includes two separate electricalmotors. One electric motor is coupled by a belt to the outer member androtates the outer member at a desired nominal rotational velocity. Thesecond motor is carried within the rotating exterior member and rotatesthe inner member at the desired higher velocity, twice that of theexterior member.

U.S. Pat. No. 4,109,855 to Brown et al. entitled "Drive System ForCentrifugal Processing Apparatus" discloses yet another drive system.The system of the Brown et al. patent has an outer shaft, affixed to theouter member for rotating the outer member at a selected velocity. Aninner shaft, coaxial with the outer shaft, is coupled to the innermember. The inner shaft rotates the inner member at twice the rotationalvelocity as the outer member. A similar system is disclosed in U.S. Pat.No. 4,109,854 to Brown entitled "Centrifugal Apparatus With OuterEnclosure".

Centrifuges of the type disclosed in the above identified Brown et al.and Brown patents can be utilized in combination with a sealed fluidflow transfer set of the type disclosed in U.S. Pat. No. 4,379,452 toDeVries. The disclosure of the DeVries patent is incorporated herein byreference. The set of the DeVries patent incorporates a blood collectioncontainer that has a somewhat elongated shape similar to those ofstandard blood collection sets. One embodiment of this combined systemis the CS3000 cell separator system marketed by Travenol Laboratories,Inc.

The CS3000 incorporates a dual member centrifuge in combination with asealed set of the type disclosed in DeVries. This is a continuous systemthat requires the donor to receive two needle punctures. Such systemshave been extensively used in blood centers for plasma and plateletpheresis.

The CS3000 is a large and expensive unit that is not intended to beportable. Further, the DeVries type transfer sets are quite complex toinstall and use. They are also an order of magnitude more expensive thana standard, multi-container blood collection set.

A further alternate to the Adams structure is illustrated in U.S. Pat.No. 4,530,691 to Brown entitled "Centrifuge With Movable Mandrel." Thespecification and figures of this Brown patent are hereby incorporatedby reference herein. The centrifuge of this latter Brown patent also isof the Adams-type. However, this latter centrifuge has an exteriormember which is hinged for easy opening. When the hinged upper sectionis pivoted away from the bottom section, it carries the rotatable innermember along with it.

The inner member supports a receiving chamber with a spring biasedmandrel which continually presses against a sealed, blood containingcontainer positioned within the receiving chamber. The system of thislatter Brown patent also discloses the use of two separate electricmotors to rotate the inner and outer members. The motors are coupled toa control system.

There thus continues to be a need for methods and related apparatus ofplatelet or plasmapheresis which can readily be used with volunteerdonors at various temporary locations. This method and related apparatusshould be usable by technicians with a level of skill commensurate withthe level of skill now found at volunteer-based blood collectioncenters. Further, both the method and related apparatus should bereadily portable to locations such as churches or schools where bloodcollection centers are temporarily established. Preferably the apparatuswill be essentially self-contained. Preferably, the equipment needed topractice the method will be relatively inexpensive and the bloodcontacting set will be disposable each time the plasma has beencollected from a single donor.

SUMMARY OF THE INVENTION

In accordance with the invention, a method is provided of continuouslyseparating a selected component from a fluid. The method includesproviding an elongated flexible separation chamber which has an inputport. The separation chamber or member has at least one output port.

A first fluid flow conduit, a plastic tubing member for example, iscoupled at one end to the input port. A second fluid flow conduit, alsoa plastic tubing member, is coupled to the output port.

A centrifuge is provided which has a hollow cylindrical receivingchamber. The separation member is placed in the receiving chamberadjacent an interior curved peripheral wall thereof. Distal ends of thetwo tubing members are brought out to a fixed location.

The centrifuge, including the receiving chamber is then rotated atpredetermined first and second rates. Simultaneously, an input fluidflow is provided at the fixed distal end of the first fluid flowconduit. The input fluid flow partly fills the separation member. Theinput fluid is separated in the separation member by centrifugal forces.An interface is formed between a portion of the separated fluidcomponent and a portion of the residual fluid. The interface is formedadjacent a selectively oriented surface of the receiving chamber.

The location of the interface on the surface is sensed. A portion of theseparated component is withdrawn through the output port via the secondfluid flow conduit and out the fixed distal end thereof in response tothe interface being sensed at a predetermined location.

The withdrawing step can include pumping the separated fluid componentthrough the second fluid flow conduit. The separated component can thenbe accumulated in a component container.

In one embodiment of the invention, a blood collection and componentseparation set is provided. The set includes an elongated flexibleseparation chamber which is formed with at least one interface regionthereon. The interface region is, at least in part, transmissive ofradiant energy. The chamber has a whole blood input port, a separatedcomponent output port and a residual fluid output port. The separatedcomponent can be for example plasma or platelets.

First, second and third fluid flow conduits are provided, each of which,for example being a plastic tubular member. Each fluid flow conduit hasa proximal end coupled to a respective input or output port of theseparation chamber.

The first fluid flow conduit is coupled to the whole blood input port. Adistal end thereof can in turn be coupled to donor collection meanswhich can include a piercing cannula. The second fluid flow conduit iscoupled to the selected component output port. A distal end thereof canbe coupled to a collection container. The third fluid flow conduit iscoupled to the residual fluid output port.

In accordance with this embodiment of the invention, a quantity of wholeblood can be withdrawn from a donor and drawn into the separationchamber. The whole blood can be separated into plasma or platelets andpacked red blood cells in the separation chamber. The plasma orplatelets can be drawn off or pumped into the component collectioncontainer. The packed red blood cells can then be collected or returnedto the donor. The process can then be repeated a number of times untilthe desired quantity of plasma or platelets has been collected.

This embodiment requires that the donor only receive a single needlepuncture. In addition, if the concentrated red blood cells and plasmaare to be returned to the donor, the donor is never physicallydisconnected from the pheresis system until that return process has beencompleted.

In yet another embodiment of the invention, platelets can be separatedfrom the plasma and collected in a second component collectioncontainer. In this embodiment, the platelets can be accumulated in theseparation chamber while the plasma is being drawn off. Subsequently,after the plasma has been drawn off the platelets can be drawn off andcollected.

The blood collection set can be formed with a single cannula which isused for both drawing whole blood and returning packed red blood cellsto the donor. Alternately, if desired, the set can be configured as atwo cannula set with one cannula used for withdrawing whole blood and asecond cannula used for returning packed red blood cells to the donor.

In yet another embodiment of the invention, the separation chamber canbe formed in two parts. The first part can include the whole blood inputport and the packed red blood cell output port. This first part is influid flow communication with a second part. Platelet rich plasmaseparated from the whole blood in the first part flows into the secondpart and is in turn separated from the platelets therein. The plasma canthen be drawn off into a collection container or returned to the donoralong with the red blood cells. The platelets can continue to accumulatein the second part. Additional quantities of whole blood can be drawnfrom the donor and passed through the separation chamber. Subsequently,the collected platelet concentrate can be sealed in the second part.

The receiving chamber in the dual member centrifuge can be formed withan annular slot. The slot receives and supports the elongated separationchamber.

Numerous other advantages and features of the present invention willbecome readily apparent from the following detailed description of theinvention and the embodiments thereof, from the claims and from theaccompanying drawings in which the details of the invention are fullyand completely disclosed as a part of this specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view, fragmented and partly in section of a systemand method of pheresis in accordance with the present invention;

FIG. 2 is an enlarged sectional view of the receiving chamber of FIG. 1;

FIGS. 3A and 3B illustrate schematically a particular transfer set andmethod of pheresis in accordance with the present invention;

FIG. 4 is a sectional view taken along plane 4--4 of FIG. 3B;

FIG. 5A is a top plan view of a separation chamber in accordance withthe present invention illustrating the pheresis process;

FIG. 5B is a perspective view of the separation chamber and pheresisprocess illustrated in FIG. 5A;

FIG. 5C is a perspective view of an alternate embodiment of theseparation chamber illustrating the pheresis process therein;

FIG. 6 is a graph of varying hematocrit of fluid in a rotatingseparation chamber as a function of distance along the separationchamber in accordance with the present invention;

FIG. 7A is a top plan view of an alternate separation chamber inaccordance with the present invention;

FIG. 7B is a perspective view of the alternate separation chamber ofFIG. 7A;

FIG. 8 is a schematic fluid flow circuit illustrating an alternativefluid flow transfer set and method of practicing the present invention;

FIG. 9 is a schematic perspective view of a two part separation chamber;

FIG. 10 is a schematic fluid flow circuit illustrating an alternativefluid flow transfer set and method of practicing the present invention;and

FIG. 11 is a schematic fluid flow circuit illustrating an alternativefluid flow transfer set and method of practicing the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

While this invention is susceptible of embodiment in many differentforms, there is shown in the drawing and will be described herein indetail specific embodiments thereof with the understanding that thepresent disclosure is to be considered as an exemplification of theprinciples of the invention and are not intended to limit the inventionto the specific embodiments illustrated.

FIG. 1 illustrates a readily transportable system 10 in accordance withthe present invention. The system 10 includes a relatively light-weightdual member centrifuge 12 and an associated fluid flow transfer set 14.

The dual member centrifuge 12 is of the Adams type having a stationarysupport 20 on which is mounted a first motor 22. The first motor 22 hasa rotary output shaft 24 which rotates at a first angular velocityconventionally referred to as one omega. Fixedly attached to the rotaryshaft 24 is a yoke 26. The yoke 26 supports a second electric motor 28.The electric motor 28 has a rotary output shaft 30. The shaft 30 rotatesat an angular velocity twice that of the shaft 24, conventionallyreferred to as two omega. The motor 28 is pivotably attached to the yoke26 at pivot points 36 and 38.

Affixed to the rotating shaft 30 is a cylindrical receiving chamber 40.The details of the chamber 40 are illustrated in detail in FIG. 2. Thereceiving chamber 40 is rotated by the shaft 30. The chamber 40 includesa region 40a that is transparent to selected, incident radiant energy.The chamber 40 has a cylindrical exterior peripheral region 42. Spacedapart from the exterior region 42 is a generally cylindrical interiorperipheral region 44. Between the exterior region 42 and the interiorregion 44 is a selectively shaped annular slot 46. The slot 46 has aclosed end 46a. The slot 46 slidably receives a separation chamber 50.The chamber 40 has an exterior diameter on the order of six inches andan internal length on the order of 2.3 inches. The slot 46 has a lengthon the order of 2.1 inches. The width of the slot 46 is on the order of0.2 inches.

The separation chamber 50 is in fluid flow communication via a flexiblemulti-channel conduit 52 with the remainder of the set 14. A proximalend 54 of the flexible fluid flow conduit 52 is coupled to theseparation chamber 50.

The fluid flow conduit 52 is supported by a stationary torque arm 56.The use of such torque arms is well known to those skilled in the use ofdual member centrifuges of the Adams type. A distal end 60 of the fluidflow conduit 52 separates into a plurality of discrete flexible conduits60a, 60b and 60c. The distal ends 60a, 60b and 60c are each in fluidflow communication with a respective container as seen in FIGS. 3a and3b.

The conduits 60a, 60b and 60c could be formed of various flexible,medical grade plastics.

The system 10 also includes a control system 66 which is coupled to themotors 22 and 28. Control systems for use with dual member centrifugesof the Adams type are known in the art. One type of suitable controlsystem is a proportional-integral-differential control system. Variousof the above noted patents disclose a variety of ways to rotate andcontrol dual member centrifuges.

The control system 66 receives feedback from vibration and fluid leaksensors 68 and 70. The sensors 68 and 70 are fixedly supported by astationary suspension system 72. The system 72 can be connected toresilient members 74 to stabilize the centrifuge 12 during operation.

A source of radiant energy 76 is affixed to the 2 ω motor 28. The source76 directs a beam of radiant energy 76a toward the radiant energytransmitting region 40a of the rotatable chamber 40. The region 40apermits the beam of radiant energy 76a to inpinge on an interface regionof the separation chamber 50. A portion 76b of the beam 76a will passthrough the interface region of the separation chamber 50 and emerge tobe detected at an interface sensor 80.

The source 76 could be any emitter of radiant energy such as infrared orincandescent light. The sensor 80 could be any compatible energysensitive detector. The interface sensor 80 can be used to detect thelocation of the interface between the separated plasma and packed redblood cells in the separation chamber 50 during the centrifugationprocess. The sensor 80 is also coupled to the control system 66.

FIG. 2 illustrates the shape of the slot 46 in the receiving chamber 40.The slot 46 has two spaced apart annular surfaces 46b, 46c. This spacingis on the order of 0.2 inches. The slot 46 has a downwardly orientedopening 46d. The separation chamber 50 is slid into the slot 46 via theopening 46d. If necessary, the opening 46d can be covered by a metalcover to initially retain the separation chamber 50 in position. Oncethe chamber 40 is rotated and the chamber 50 has been filled with fluid,the rotational forces set up adequate frictional forces such that theseparation chamber 50 will be locked in place.

The chamber 40 can be molded of polycarbonate, a transparent plastic.The radiant energy beam 76a readily passes through this material. Thechamber 40 can be selectively painted or masked so as to limit thoseregions through which the radiant energy 76a can pass.

FIGS. 3a and 3b schematically illustrate the details of the fluidtransfer set 14 as well as one mode of using same. In FIGS. 3a and 3barrows along a conduit or tubing member indicate a direction of fluidflow.

The set 14 in addition to the separation chamber 50 and themulti-channel conduit 52 includes a whole blood collection container 86.Attached to the collection container 86 is a draw conduit 88 whichterminates at a free end in a draw cannula 88a. The draw cannula 88a isintended to be inserted into a vein of a donor. The set 14 also includesa plasma collection container 90 and a red blood cell nutritivecontainer 92.

The solution in the container 92 is of a known type which providesnutrients to packed red blood cells subsequent to the plasma pheresisprocess. Contents of such solutions include dextrose, sodium chloride,mannitol and adenine. One appropriate solution is marketed by TravenolLaboratories, Inc. under the trademark ADSOL. The container 92 is sealedwith a frangible member 92a which can be broken at an appropriate pointin the plasma pheresis process.

The set 14 is initially used to collect a unit of blood in the wholeblood collection container 86 using standard procedures. Once the unitof whole blood 86 has been collected, the cannula 88a is removed fromthe arm of the donor and the tubing 88 is closed by heat sealing. Theset 14 is now a closed sterile system. The separation chamber 50 ispositioned in the slot within the rotatable receiving chamber 40. Theseparation chamber 50 can then be rotated.

A whole blood pump 94 can be utiiized to meter whole blood from thecontainer 86 into the chamber 50 for separation into concentrated redblood cells and plasma. The plasma can be withdrawn after separationinto the container 90. A second pump 96 can be used to pump theconcentrated red blood cells into the container 92 containing thenutritive solution. The containers 90 and 92 can then be closed by heatsealing and separated from the remainder of the set 14.

While the set and method illustrated in FIGS. 3a and 3b are primarilysuited for processing of whole blood on a batch basis, one of theadvantages of the present invention lies in the fact that it should bepossible to separate to a great extent the white cells from the plasma.It is known that from time to time the white cells from a donor infusedinto a receipient can cause an adverse reaction. Hence, removal of thesewhite cells would be both desirable and beneficial.

In a preferred mode, the separation chamber 50 has a volume on the orderof 80 to 90 ml. The preferred separation centrifugation speeds are in arange on the order of 3800 to 4200 rpm.

FIG. 4, a sectional view taken along plane 4-4 of FIG. 3b, illustratesthe overall shape of the chamber 50 prior to the centrifugation process.The chamber 50 can be formed of a single plastic sheet member. Thatmember is folded on itself and sealed in a region 51. An internal volume51a results. The fluid being separated flows in this volume.

FIGS. 5A through 5C schematically illustrate the separation process asthe separation chamber 50 is being rotated. As is illustrated in FIGS.5A-5C the chamber 40 and the separation chamber 50 are rotated in adirection 100. Whole blood is infused at the input port 50a and flowsinto the separation chamber 50 in a direction 102. The whole blood inputport 50a is positioned centrally with respect to the centrifugal forcefield F.

Under the influence of the centrifugal force field F, the whole bloodseparates into high density packed red blood cells in an outer annularregion 104 adjacent the maximum centrifugal force region 42 of therotatable chamber 40. Lower density plasma separates out into an innerannular region 106 adjacent a relatively lower centrifugal force regionadjacent the inner region 44. Between the outer annular region 104 ofpacked red blood cells and the inner annular region 106 of plasma, asubstantially smaller layer 108 of platelets forms.

A surface 110 can be provided which is at a predetermined angle withrespect to the direction of flow 102. The surface 110 provides a verysharp and highly transmissive interface between the region of plasma 106and the region of packed red blood cells 104. The incident radiantenergy 76a passes through the surface member 110, which is essentiallytransparent thereto, and out the transparent region 40a of the chamber40 as the output radiant energy beam 76b. When sensed by the interfacesensor 80 the precise location of the interface between the plasma inthe region 106 and the packed red blood cells in the region 104 can bedetermined.

The output port 50b for the platelet rich plasma is located adjacent thelow force inner surface 50d of the separation chamber 50. Platelet poorplasma can be withdrawn therefrom under the control of the controlsystem 66 in response to the sensed position of the interface betweenthe red blood cells and the plasma on the surface 110.

The residual fluid output port 50c from which the packed red blood cellscan be withdrawn is positioned adjacent the relatively high force outersurface of the separation chamber 50 adjacent the outer peripheralsurface 40a.

The transparent surface 110 can be formed as part of the separationchamber 50. Alternatively, the surface 110 can be affixed to therotatable chamber 40. In this instance, a region of the chamber 50 canbe positioned adjacent thereto.

Depending on the location of the annular region 108 of platelets withrespect to the surface 110, the system 10 can operate in severaldifferent modes.

If the location of the region 108 has moved adjacent an interior end110a of the surface 110, the platelets will spill through the port 50bresulting in platelet rich plasma as the separated fluid component.

If the region 108 is centrally located as in FIG. 5A, platelets willaccumulate in the chamber. Platelet poor plasma will then flow out theport 50b. In this mode, the plasma continually flows inwardly throughthe platelet region 108. This fluidizes the platelets and minimizessedimenting and aggregating of the platelet concentrate.

In a third mode of operation, the platelet region 108 can be positionedadjacent an outer region 110b. In this instance, the platelets will beswept out of the chamber, via the port 50c with the packed red bloodcells.

As illustrated in FIG. 5C, a dam 112 can also be provided adjacent theplasma output port 50b. As is discussed subsequently, the dam 112 iseffective to retain a fluid, such as air, in the chamber 50 during startup of the centrifugation process.

As was the case with the surface 110, the dam 112 can be integrallyformed with either the separation chamber 50 or can be formed as part ofthe rotatable chamber 40.

It will be understood that FIGS. 5a through 5c are schematic in natureand are intended to illustrate the separation process. The shape of theseparation chamber 50 during the pheresis operation will be determinedby the shape of the slot 46.

The graph of FIG. 6 illustrates the expected change of hematocrit aswhole blood is infused through the input port 50a and travels along therotating separation chamber 50. Assuming an input hematocrit on theorder of 0.45, the hematocrit of the output packed red blood cellsranges between 0.80 and 1.0. One of the functions of the nutritivemixture provided in the container 92 is to restore the hematocrit of thepacked red blood cells to a value such that infusion into a receipientis possible.

FIGS. 7A and 7B illustrate schematically an alternate separation chamber51. In the separation chamber 51, whole blood is injected into thechamber at a centrally located input port 51a. Unlike the separationchamber 50, an output port 51c for the concentrated red blood cells isprovided at the same end of the chamber 51 as is the whole blood inputport 51a. In this embodiment, the red blood cells are withdrawn in theopposite direction as the input flow of the whole blood. The output port51c is located adjacent the high force outer peripheral wall of theseparation chamber 51. Thus, there are two directions of flow of fluidwithin the chamber 51.

The chamber 51 also includes a supplemental ramp 111 to urge or push thepacked cells towards the packed cell removal port 51c. This flow isopposite the flow of whole blood 51a. The ramp 111 may be integrallyformed as part of the separation chamber 51. Alternately, the ramp 111can be formed as part of the rotatable member 40.

FIG. 8 illustrates yet another system 120 which incorporates theelongated flexible separation chamber 50. The system 120 is acentrifugely based pheresis system which can provide as a separatedcomponent from whole blood either platelet poor plasma or plateletconcentrate.

The system 120 includes a fluid flow transfer set 122 which is useablein conjunction with the dual member centrifuge 12. The transfer set 122includes the draw conduit 88 with the associated cannula 88a. In the set122, the cannula 88a is used for drawing whole blood from a donor andfor returning concentrated red blood cells and/or plasma to the donorduring the pheresis operation. The system 120 is intended to be coupledto the donor continuously throughout the entire pheresis operation.

The draw/return conduit 88 is coupled at a junction connector 124 torespective tubing lines 126, 128 and 130. The tubing member 126 iscoupled via an anticoagulant pump 132 to a container of anticoagulant134. The tubing member 128 is coupled via a connector 136 and a feedblood pump 138 to the whole blood input port 50a of the separationchamber 50.

The separated component output port 50b of the separation chamber 50 iscoupled via a tubing member 140 to a plasma pump 141. A tubing member142 is coupled alternately either to a separated component container 144or a tubing member 146. The member 146 feeds either a reservoir 148 or abubble tap/bubble detector, 150 in the return conduit line 130. Clamps 1through 6 would be manually opened and closed to regulate the desireddirections of flow.

The residual output port 50c is coupled via a tubing member 147 and ajunction member 149 to the bubble trap/bubble detector 150.

In operation, the set 122 would be coupled to the donor by means of thecannula 88a. The chamber 50, as previously discussed, would bepositioned in the receiving chamber of the dual member centrifuge 12.Clamps 1, 4, and 5 would be opened. Clamps 2, 3 and 6 would be closed.

Whole blood would be drained from the donor via conduit 128.Anticoagulant would be simultaneously infused into the whole blood viathe conduit 126. The feed blood pump 138 would draw the blood from thedonor at approximately a 70 ml per minute rate. The pump 138 would alsosupply the drawn blood to the input port 50a of the rotating separationchamber 50 at the same rate.

The rotating separation chamber 50 would separate the whole blood intoplatelet poor plasma at the output port 50b and red blood cells at theoutput port 50c. Red blood cells from the output port 50c would beaccumulated in the reservoir 148 simultaneously with platelet poorplasma being accumulated in the container 144.

When the volume and weight detector associated with the reservoir 148indicates that a maximum extracorporeal volume has been accumulatedtherein, clamps 1, 4 and 5 would be closed. Clamps 2, 3 and 6 would beopened.

The concentrated cells in the reservoir 148 would be pumped, via thefeed pump 138, through the separation chamber 50 a second time. Outputfrom the separation chamber 50 via conduits 140 and 147 would be passedthrough the bubble trap 150 and, via the conduit 130, returned throughthe cannula 88a to the donor. When the weight and volume detectorindicated that the reservoir 148 was sufficiently empty, the drawprocess would be reinitiated.

Hence, the system 120 would be capable of accumulating platelet poorplasma in the container 144. In addition, the platelets would beaccumulated in the region 108 of the separation chamber 50. Subsequentto the plasma having been collected, the container 144 can be replacedand the platelets could be drawn off and accumulated in the replacementcontainer.

Densities of platelets which could be accumulated and drawn off in thisfashion range from 200 billion to 300 billion cells in 100 ml of fluid.Such densities might take 3 to 4 cycles of whole blood drawn from thedonor to build up the necessary platelet concentration in the separationchamber 50.

Alternately, the platelet poor plasma could be pumped into the reservoir142 and returned after the second pass to the donor. The plateletconcentrate can then be accumulated in the container 144.

FIG. 9 illustrates yet another separation chamber 160. The separationchamber 160 has two fluid separating portions 162 and 164. The fluidseparating portion 162 includes a whole blood input port 162a centrallylocated at an input end of the portion 162. A concentrated red bloodcell output port 162c is also provided adjacent the input port 162a. Theportion 162 thus includes whole blood flowing into the region and packedred blood cells flowing out of the region. The portion 162 could have arelatively small volume on the order of 20-30 ml.

Separated platelet rich plasma can be drawn out of the portion 162 via aconduit 166. The platelet rich plasma can then be separated in thesecond portion 164 into platelet poor plasma and platelets. Theplatelets accumulate in the second portion 164 along the outer, highforce, wall 164a. The second portion 164 includes an output port 162b.The platelet poor plasma can be returned to the donor. The portion 164can have a volume on the order of 50-60 ml.

FIG. 10 illustrates a system 170 usable for platelet pheresis. Thesystem 170 incorporates a single use disposable fluid transfer set 172.The set 172 includes the two part separation chamber 160 of FIG. 9.Other elements of the set 172 which correspond to elements of thepreviously discussed set 122 have been given identical identificationnumerals.

The two part chamber 160 would be positioned in the receiving chamber ofthe dual member centrifuge 12. Clamps 1, 4 and 6 would be opened. Clamps2, 3 and 5 would be closed. The set 172 could be mounted on an automatedfixture which could automatically operate the clamps 1-6.

In operation, the set 172 would be coupled to the donor by means of thecannula 88a. Whole blood would be drawn from the donor by the cannula88a. The whole blood will flow through the conduit 88, the conduit 128and, via the feed blood pump 132, would be pumped into the input port162a of the separation chamber 160 at a 70 ml per minute rate.

Concentrated red blood cells from the output port 162c would flow intothe reservoir 148 via the conduit 147. Platelet rich plasma, via thetubing member 166 will flow into the rotating platelet separationchamber 164. Output from the platelet separation chamber 164, via theoutput port 162b will be platelet poor plasma. The platelet poor plasmawill be pumped via the plasma pump 141 in the conduit 146 into thereservoir 148. While the whole blood is passing through the separationchamber portion 162 and the platelet poor plasma is being separated inthe platelet chamber 164, platelets will continue to accumulate in thechamber 164.

When the volume and weight detector associate with the reservoir 148indicates that a maximum extracorporeal volume of drawn blood hasaccumulated in the set 172, the appropriate detector signal will begenerated. The operator or fixture will then close clamps 1 and 4. Theoperator or fixture will open clamps 2 and 3. Fluid in the reservoir 148will be pumped via the feed pump 138 through the separation chamber 160a second time. This fluid includes plasma and packed red blood cellswhich had previously accumulated therein thus providing a secondopportunity to collect those platelets not collected with the firstpass. However, with clamp 4 closed, output fluid on the line 147 and theline 166 will pass through the bubble trap/bubble detector 150 throughthe line 130 and be returned to the donor via conduit 88 and cannula88a.

When the reservoir 148 has been sufficiently emptied, the volume weightdetector will again generate a indicator signal. The operator or fixturewill reclose clamps 2 and 3 and reopen clamps 1 and 4 to reinitiate thedraw cycle. Whole blood will again be drawn from the donor at the 70 mlper minute rate. This process may be repeated as many times as desiredso as to accumulate the desired quantity of platelets in the chamber164.

Subsequent to the desired quantity of platelets having been accumulatedin chamber 164, clamps 1, 3 and 6 can be closed and clamp 5 can beopened. The platelets must then be resuspended, for example, by shakingthe platelet chamber 164. Platelets can be pumped from the chamber 164by the pump 141 into the platelet accumulation container 174. By meansof this process, platelets on the order of 4×10¹¹ cells can beaccumulated from a single donor. This represents approximately 90percent of the platelets which were in the blood drawn from the donor.

FIG. 11 illustrates an alternate system 180 which incorporates adisposable fluid flow transfer set 182. The transfer set 182 includesthe draw return cannula 88a and associated conduit 88. Whole blood isdrawn through and concentrated cells are returned through a conduitmember 184 which is coupled to an input to the bubble trap/bubbledetector 150. Output from the bubble trap/bubble detector 150 via abidirectional pump 186 flows into a reservoir 188 at an input port 188b.A deflector member 188d in the container 188 directs and regulates theflow of fluid among the ports 188a, 188b and 188c.

During the draw cycle, whole blood which flows through the conduit 184,the conduit 184a and into the input port 188B of the reservoir 188 isdeflected by the member 188D and flows out the port 188A. Output wholeblood flow from the port 188A via a conduit 189 is pumped by the feedpump 190 at a flow rate of 70-80 ml per minute into the input port 162aof the two part separation chamber 160.

Red blood cells separated in the chamber 162 flow via conduit 192 intothe input port 188C of the reservoir 188 and are accumulated therein.Assuming clamp 2 is closed and clamp 1 is open, platelet poor plasmaseparated in the platelet chamber 164 flows via the output port 162b andthe pump 141 through a fluid flow conduit 194 also into the reservoir188.

In operation, set 182 would be coupled to the donor by means of thecannula 88a. The chamber 160 would be positioned in the receivingchamber of the dual member centrifuge 12. Clamp 1 would be opened andclamp 2 would be closed.

Whole blood would then be drained through the conduit 184 as discussedabove at a 70 to 80 ml per minute rate. When the reservoir 188 is filledwith a predetermined maximum extracorporeal volume, the volume/weightdetector will generate an appropriate signal. At such time, thebidirectional donor pump 186 will be reversed. Fluid will then be drawnfrom the reservoir 188 out the port 188B via the fluid flow conduit 184aand the bubble trap/bubble detector 150 to the fluid flow conduit 184.The fluid will then be returned to the donor via the conduit 88 and thecannula 88a.

The return rate of the concentrated cells, including red blood cells andplasma, is on the order of 130 to 150 ml per minute. This substantiallyincreased return fluid flow rate provides the important advantage inthat the time necessary to return the concentrated cells to the donor isapproximately half of the time required for the draw cycle. While theconcentrated cells are being returned to the donor, fluid continues tobe pumped from the reservoir 188 via the port 188a via the feed pump 190through the separation chamber 160 and back to the donor via the port188c. Additional volume flow rate can come directly from the reservoir188. Platelets continue to accumulate in the chamber 164.

The draw cycle can then be reinitiated and an additional quantity ofblood drawn from the donor. When the desired quantity of platelets hasbeen accumulated in the chamber 164, clamp 1 can be closed and clamp 2can be opened. The platelets then need to be resuspended. By means ofthe pump 141, the platelets in the chamber 164 can then be pumped intothe container 198. Quantities of platelets on the order of 4×10¹¹ cellscan be accumulated using the system and apparatus in FIG. 11 in a timeinterval on the order of 50 minutes.

With respect to the embodiment of FIG. 5C, the use of the dam or shim112 illustrated therein allows priming of a dry fluid transfer systemwith whole blood and prevents the occurence of potential air locks whichwould hinder the flow of plasma and/or platelets in the fluid flowconduits during high speed centrifugation. The shim or dam 112, as notedpreviously, can be formed as part of the separation chamber 50.Alternately, it can be formed as part of the rotatable receiving chamber40.

Many of the known cell separation systems require saline priming of theseparation chambers prior to the pheresis operation. As a result, it isnecessary to supply a container of sterile saline as part of thetransfer set. During set up, a frangible in the saline container isbroken permiting the saline to flow into the separation chamber drivingout any air present therein and providing a liquid filled separationchamber.

The separation chamber 50 of FIG. 5C does not require the use of salinefor priming. The various ports have been located on the separationchamber 50, taking into account different fluid densities. The ports arelocated in different planes of the centrifugal force field F. Forexample, the input whole blood port 50A is centrally located withrespect to the force field. The plasma output port 50B is locatedadjacent the relatively low force interior wall of the separationchamber 50. The residual fluid output port 50C for the concentrated orpacked red blood cells is located adjacent the maximum force exteriorwall of the separation chamber 50.

Directing of the fluids to the various output ports is accomplished bymeans of essentially rigid deflecting members such as the shim or dam112 adjacent the separated component or plasma output port 50B. A shimor dam 112A is associated with the concentrated red blood cell outputport 50C. The interface surface 110 which is illustrated in FIG. 5Cformed as part of the outer wall 40a of the receiving chamber 40 directsthe flow of separated plasma cells.

The dams or shims 112 and 112A are also effective to prevent the flow ofair through the plasma port. Since air has a lower density then plasma,a certain amount of air will remain in the inner most region of theseparation chamber 50. This air is also compressed at higher centrifugespeeds.

The problem posed by air in the system is a result of pressures inducedby the centrifugal force field F. These forces are proportional to thesquare of the radius of the receiving chamber as well as the square ofthe rotational velocity of the receiving chamber and the separationchamber 50 along with the density of the fluid. If air gets into thefluid flow conduit associated with the output port 50B, a pressure dropwill occur in that line. This pressure drop may force the plasma pump toclamp the tubing shut and stop the flow of plasma by requiring too higha vacuum in the conduit. Alternately, the pump may degas the plasma.

Overcoming this condition requires that the receiving chamber 40 andseparating chamber 50 be slowed down until the plasma pump can overcomethis pressure drop. Hence, the use of the saline in the known devices todrive all of the air out of the separation chamber and the related fluidflow conduits. On the other hand, in the embodiment of FIG. 5C the shimsor dams 112 and 112a prevent movement of the air out of the separationchamber 50 by creating a reservoir which will trap the air within thechamber during a low speed prime with blood. At high speed operation,the centrifugal induced pressure will compress this air away from thedam 112. The presence of a small amount of air in the chamber will notinterfere with the pheresis process as long as the air is not permittedto escape into the fluid flow conduits associated with the output portof the chamber.

From the foregoing, it will be observed that numerous variations andmodifications may be effected without departing from the true spirit andscope of the novel concept of the invention. It is to be understood thatno limitation with respect to the specific apparatus illustrated hereinis intended or should be inferred. It is, of course, intended to coverby the appended claims all such modifications as fall within the scopeof the claims.

What is claimed is:
 1. A chamber for use in a rotating field to separatewhole blood into red blood cells and a plasma constituent comprisingwallmeans for defining first and second radially spaced apart walls forminga separation zone, the first wall comprising a low-G side of theseparation zone located a first radial distance from the rotationalaxis, the second wall comprising a high-G side of the separation zonelocated a second radial distance from the rotational axis are greaterthan the first radial distance, the the separation zone including aninlet region, a first port in the inlet region for conveying whole bloodinto the inlet region in a first flow direction to begin separation intored blood cells toward the high-G side of the separation zone and theplasma constituent toward the low-G side of the separation zone, asecond port on the high-G side of the inlet region for collecting redblood cells from the high-G side of the separation zone, and theseparation zone being free of slope along the axis of rotation in thefirst flow direction, the second radial distance of the second wall fromthe rotational axis decreasing in the first flow direction from theinlet region while the radial spacing between the first and second wallsdecreases in the first flow direction in the inlet region forming atapered ramp in the inlet region for urging red blood cells along thehigh-G side to flow toward the second port in a second flow directionopposite to the first flow direction.
 2. A chamber according to claim1wherein the first port is located in the inlet region between the low-Gside and the high-G side of the separation zone.
 3. A chamber accordingto claim 1wherein the chamber has an elongated axis that extendscircumferentially about the rotational axis, wherein the first port hasan axis that extends generally parallel to the elongated axis of thechamber.
 4. A chamber according to claim 3wherein the second port has anaxis that extends generally parallel to the elongated axis of thechamber.
 5. A chamber according to claim 1and further including aninterior surface located, relative to the first flow direction,downstream of the inlet region, the surface extending into theseparation zone at a selected angle relative to the first flowdirection.
 6. A chamber according to claim 5wherein the tapered rampjoins the interior surface adjacent the high-G side and extendstherefrom along the second side wall in the second flow direction towardthe second port.
 7. A chamber according to claim 5wherein the interiorsurface ends in the first flow direction from the second wall toward thefirst wall at a non-perpendicular angle.
 8. A chamber according to claim7wherein the tapered ramp joins the interior surface along the secondwall and extends therefrom toward the second port.
 9. A chamberaccording to claim 5and further including a third port located, relativeto the first flow direction, downstream of the interior surface forcollecting the plasma constituent in the low-G side of the separationzone.
 10. A chamber according to claim 5and further including a secondsurface, offset from the interior surface, for restricting the flow ofplasma constituent.
 11. A chamber according to claim 10and furtherincluding a third port located, relative to the first flow direction,downstream of the second surface for collecting the plasma constituentin the low-G side of the separation zone.
 12. A chamber according toclaim 10wherein the third port is located, relative to the first flowdirection, downstream of the inlet region.
 13. A chamber according toclaim 1and further including a third port for collecting the plasmaconstituent in the low-G side of the separation zone.